The author, a psychiatric epidemiologist, proposes to acquire skill in the field of genetics in order to combine the methods of genetics and epidemiology which heretofore have generally been applied independently to data on complex human disorders. The major long-term goal specified in this proposal is to conduct research on environmental and genetic risk factors for major affective illness. Results of genetic studies of transmission of affective illness have been inconclusive because of imprecise definitions of the illness, the role of social risk factors has been inadequately quantified, and the high degree of assortative mating among patients with affective disorder has obscured patterns of transmission. The following research goals are proposed so that more accurate estimates of both genetic and cultural contributions to the liability for affective illness can be made: a. Define homogeneous categories of major affective illness using a combination of epidemiologic and genetic approaches to analyze the data. b. Study the effects of assortative mating on transmission of affective illness by developing new approaches to incorporating non-random mating in genetic analyses and examining the environmental effects of dual mating; and c. Examine the role of gene-environmental interaction in the pathogenesis of affective illness. In order to achieve the research goals, the following goals for supervised research and development are proposed: 1) to learn gene mechanisms at an introductory level; 2) to gain an understanding of the statistical principles and assumptions which are necessary to conduct genetic analyses; 3) to learn the theory and application of the major methods of genetic analysis; 4) to learn about the various types of population studies which are used to elucidate genetic mechanisms; 5) to become familiar with the current state of the field of genetics in incorporating environmental factors and non-random mating; and 6) to study diverse approaches to establishing validity of diagnostic categories.